1AGN

X-RAY STRUCTURE OF HUMAN SIGMA ALCOHOL DEHYDROGENASE

Summary for 1AGN

• Entry DOI: 10.2210/pdb1agn/pdb
• Descriptor: HUMAN SIGMA ALCOHOL DEHYDROGENASE, ZINC ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P40394
• Total number of polymer chains: 4
• Total formula weight: 163988.09

Authors

Hurley, T.D.,Xie, P. (deposition date: 1996-06-04, release date: 1997-03-12, Last modification date: 2024-02-07)

Primary citation

Xie, P.,Parsons, S.H.,Speckhard, D.C.,Bosron, W.F.,Hurley, T.D.
X-ray structure of human class IV sigmasigma alcohol dehydrogenase. Structural basis for substrate specificity.
J.Biol.Chem., 272:18558-18563, 1997

PubMed Abstract: The structural determinants of substrate recognition in the human class IV, or sigmasigma, alcohol dehydrogenase (ADH) isoenzyme were examined through x-ray crystallography and site-directed mutagenesis. The crystal structure of sigmasigma ADH complexed with NAD+ and acetate was solved to 3-A resolution. The human beta1beta1 and sigmasigma ADH isoenzymes share 69% sequence identity and exhibit dramatically different kinetic properties. Differences in the amino acids at positions 57, 116, 141, 309, and 317 create a different topology within the sigmasigma substrate-binding pocket, relative to the beta1beta1 isoenzyme. The nicotinamide ring of the NAD(H) molecule, in the sigmasigma structure, appears to be twisted relative to its position in the beta1beta1 isoenzyme. In conjunction with movements of Thr-48 and Phe-93, this twist widens the substrate pocket in the vicinity of the catalytic zinc and may contribute to this isoenzyme's high Km for small substrates. The presence of Met-57, Met-141, and Phe-309 narrow the middle region of the sigmasigma substrate pocket and may explain the substantially decreased Km values with increased chain length of substrates in sigmasigma ADH. The kinetic properties of a mutant sigmasigma enzyme (sigma309L317A) suggest that widening the middle region of the substrate pocket increases Km by weakening the interactions between the enzyme and smaller substrates while not affecting the binding of longer alcohols, such as hexanol and retinol.

PubMed: 9228021
DOI: 10.1074/jbc.272.30.18558

Experimental method

X-RAY DIFFRACTION (3 Å)